Search

Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia. The purpose of this study was to clarify whether the effectiveness of immunotherapy in patients with suspected AICA could be predicted by anti-mouse cerebellar tissue-derived antigen antibody tests.This study was conducted on 25 patients with idiopathic cerebellar ataxia (excluding multiple system atrophy, hereditary spinocerebellar degeneration, cancer-bearing patients, and patients taking phenytoin) who received immunotherapy from 2005 to 2016 at Tokyo Medical University Hachioji Medical Center. The patients were suspected of having AICA because they were positive for cerebellar ataxia-related autoantibodies (anti-thyroid antibody, anti-GAD antibody, anti-gliadin antibody, or anti-transglutaminase 6 antibody) or other autoantibodies. Antibodies that bind to mouse cerebellar tissue-derived antigens were defined as "anti-mouse cerebellar tissue-derived antigen antibodies" in this study, and their IgG-class antibodies were comprehensively measured using a slot blot.Anti-mouse cerebellar tissue-derived antigen antibody test results were correlated with immunotherapy efficacy. Furthermore, the combination of anti-mouse cerebellar tissue-derived antigen and anti-GAD antibody tests could predict the effectiveness of immunotherapy with 83% sensitivity and 100% specificity, while the combination of the anti-mouse cerebellar tissue-derived antigen, anti-GAD, and anti-gliadin (IgA class) antibody tests could predict the effectiveness of immunotherapy with 94% sensitivity and 86% specificity.Anti-mouse cerebellar tissue-derived antigen antibody tests could help to provide useful information for immunotherapy administration to patients with idiopathic cerebellar ataxia suspected to be AICA.

The cerebellum is one of the main targets in the central nervous system for autoimmunity. Immune-mediated cerebellar ataxias include gluten ataxia, GAD antibody-associated cerebellar ataxia, Hashimoto's encephalopathy, and paraneoplastic cerebellar degeneration. Autoimmune cerebellar ataxia may be of either insidious or subacute onset, and vertigo or transient neurological symptoms occur in some patients before the onset of the disease, in contrast to spinocerebellar degeneration. If autoimmune cerebellar ataxia is suspected, early diagnosis and introduction of treatment are very important. For diagnosis, testing for gliadin antibody, TG6 antibody, GAD antibody, thyroid antibody, and anti-neuronal antibodies, including mGluR1, is useful. Magnetic resonance imaging voxel-based morphometry is also useful because it can detect cortical cerebellar atrophy of autoimmune cerebellar ataxia, different from spinocerebellar ataxia. As for treatment, it is important to remove autoimmune triggering factors (e.g.,dietary gluten or neoplasm). When the ataxia symptoms are causing hindrances in the daily life, it is worth considering immunotherapy including IVIg, steroid therapy and so on.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Gluten-related disorders (GRDs) are conditions that develop in response to the common trigger of gluten ingestion and manifest as a variety of clinical symptoms. GRDs have been considered rare in Asian countries, including Japan, because of lower consumption of wheat products than in Europe and the U.S.A. and differences in genetic background. Recently, however, GRDs, such as celiac disease and gluten ataxia, have been reported in Japan, albeit sporadically and their presence is now recognized in this country. Gluten ataxia is defined as an anti-gliadin antibody positive sporadic ataxia. Recently, it was reported that the presence of anti-transglutaminase-6 (TG6) antibody can be used to diagnose gluten ataxia. Herein, we will review evidence relating to gluten ataxia and report two cases of anti-TG6 antibody positive gluten ataxia. In patients with gluten ataxia, sensory disturbance is generally considered to be so mild that it contributes minimally to ataxia. However, our patients showed a positive Romberg sign. Deep sensory disturbance, in addition to cerebellar disturbance, may have been involved in the clinical symptoms of our cases.

An 81-year-old woman presented with a chief complaint of gait disturbance. Brain magnetic resonance imaging (MRI) showed mild cerebellar atrophy and cerebral blood flow scintigraphy revealed reduced blood flow in the cerebellum. The patient was diagnosed with cortical cerebellar atrophy, and was given taltirelin hydrate, but symptoms slowly progressed. Thirteen years after onset, a positive result for anti-transglutaminase 6 (TG6) IgA antibodies was identified, and gluten ataxia was diagnosed. Despite steroid therapy and gluten-free diet therapy, no improvements were seen, and independent walking became difficult for the patient. High-dose intravenous immunoglobulin therapy resulted in improvements in the Posture and Gait subscore of the International Cooperative Ataxia Rating Scale (ICARS) from 15 to 11 points, and the patient regained the ability to walk independently. Gluten ataxia are rarely reported in Japan and anti-TG6 antibodies were considered useful for its diagnosis.

Objective Autoimmune cerebellar ataxias were recently reported to be treatable. However, the proportion of patients with cortical cerebellar atrophy of unknown etiology with autoimmune-associated cerebellar ataxia and the actual effectiveness of immunotherapy in these diseases remain unknown. Methods We measured the level of autoantibodies (including anti-gliadin antibody, anti-glutamic acid decarboxylase (GAD) antibody, and anti-thyroid antibody) in 58 Japanese patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, cancer, or those who were receiving phenytoin, and the efficacy of immunotherapy was assessed. Results Thirty-one of 58 (53%) patients were positive for anti-GAD antibody, anti-gliadin antibody, or anti-thyroid antibody. Seven of the 12 anti-gliadin antibody-positive patients, three of the four anti-GAD antibody-positive patients, and three of the six anti-thyroid antibody-positive patients responded well to immunotherapy, indicating that 59% of patients with ataxia-associated antibody-positive cerebellar ataxia undergoing immunotherapy responded well. Conclusion Some patients with cerebellar ataxia have autoimmune conditions and diagnosing autoimmune cerebellar ataxia is therefore an important component in the care of patients with this disease entity.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

We present the case of a 51-year-old man with a 5-year history of slowly progressive gait ataxia and dysarthria who showed a wide-based gait requiring assistance. The patient's score on the Revised Hasegawa Dementia Scale (HDS-R) was 22/30 and constructional apraxia was also evident. Cerebrospinal fluid analysis showed 3 cells/microl, and the protein concentration was 58 mg/dl. Brain MRI showed no evidence of cerebellar atrophy, and SPECT-eZIS showed no decrease in cerebellar blood flow. However, voxel based morphometry (VBM) and FineSRT revealed cortical cerebellar atrophy and reduced cerebellar blood flow. In addition, the patient tested positive for anti-gliadin (IgA) and anti-SS-A/Ro antibodies, and was thus diagnosed as having autoimmune cerebellar ataxia. The patient showed positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. The HDS-R score also improved to 27/30. If cortical cerebellar atrophy can be diagnosed in the early stages in patients with progressive cerebellar ataxia by imaging techniques such as MRI-VBM and FineSRT, and if such patients test positive for anti-gliadin, anti-GAD or anti-thyroid antibodies, it is possible that they have autoimmune cerebellar ataxia. The commencement of immunotherapy including IVIg should be considered in such

Objective It has been reported that autoimmune cerebellar ataxias, such as anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia and gluten ataxia, are treatable. Here, we examined the therapeutic efficacy of intravenous immunoglobulin (IVIg) on autoantibody-positive cerebellar ataxia. Patients and Methods IVIg therapy was administered in seven autoantibody-positive cerebellar ataxia patients. Therapeutic efficacy was examined in terms of its effects on clinical symptoms and changes in brain perfusion using single photon emission computed tomography (SPECT). Results Treatment was effective in four cerebellar cortical atrophy patients (two anti-GAD antibody-positive and two anti-gliadin antibody-positive) and in one anti-thyroid antibody-positive spinocerebellar ataxia type 3 (SCA3) patient, but not in two multiple system atrophy (MSA) patients. All four IVIg effective patients who underwent SPECT showed apparent increases in cerebellar perfusion. Conclusion If cerebellar ataxia with an autoimmune mechanism is suspected and radiological findings do not reveal MSA, it is worth considering immunotherapy including IVIg.

A 70-year-old Japanese man with amyloid polyneuropathy associated with a Val 107 transthyretin (TTR) mutation is reported. The patient presented with carpal tunnel syndrome, cardiomyopathy, bulbar palsy, dysphonia and polyneuropathy. DNA analysis of the TTR gene revealed a point mutation responsible for substitution of valine for isoleucine at position 107 of the TTR molecule. Taken together with reports of patients with the same TTR variant, Val 107 TTR mutation is probably associated with a clinical phenotype characterized by carpal tunnel syndrome, cardiomyopathy, bulbar palsy and dysphonia. This case implies a worldwide distribution of the Val 107 TTR mutation with a common clinical phenotype, despite different ethnic background.

Gluten ataxia, a type of cerebellar ataxia caused by exposure to gluten in sensitive patients, has been considered common in the USA and Europe, and rare in Asia. We measured anti-deamidated gliadin peptide (DGP) antibody levels in 49 patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, or cancer, as well as those who were receiving oral administration of phenytoin. Anti-DGP antibody was positive in eight (16.3 %) patients, five of these patients were positive only for IgA, one was positive for both IgG and IgA, and two were positive only for IgG antibody. Intravenous immunoglobulin was administered to five of the eight patients, and was markedly effective in one, moderately effective in two, and ineffective in two. Steroid therapy was administered to four patients, but none had an apparent response. Ataxia symptoms improved in one patient treated with a gluten-free diet only. Although it had been thought to be extremely rare in Asia, we speculate that more than 10 % of cerebellar ataxia patients in Japan currently have gluten ataxia; therefore, measuring anti-DGP antibody or anti-gliadin antibody in cerebellar ataxia patients in Asia is important.

We evaluated atrophic sites in the brainstem and cerebellum in the patients with spinocerebellar degeneration by using voxel-based morphometry (VBM). Gray matter atrophy was found extensively in both the cerebellar hemispheres and vermis of subjects presenting the cerebellar variant of multiple system atrophy (MSA-C; n=9). In addition, remarkable white matter atrophy was observed in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. In contrast, gray matter atrophy was not apparent in the cerebellar hemispheres or vermis of subjects in the SCA3 group (n=6), whereas intense white matter atrophy was visible in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. White matter atrophy was also observed in the brainstem and surrounding the dentate nucleus in both cases of dentatorubral-pallidoluysian atrophy (DRPLA) (n=2), whereas gray matter atrophy of the cerebellum was not remarkable. In both the SCA6 group (n=3) and the SCA31 group (n=2), gray matter atrophy was prominent in the cerebellar hemispheres and vermis; however, white matter atrophy was not found in the middle cerebellar peduncle and brainstem, whereas symmetric atrophy of white matter was found in the vicinity of the dentate nucleus. In each of these diseases, VBM findings were consistent with the pathological findings; therefore, VBM can be considered a useful tool for the diagnosis of spinocerebellar degeneration.

A new method for studying brain microcirculation is described, Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy, Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 μm beneath the brain surface, The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure, Twenty-second periods of forebrain ischemia were induced using the four-vessel occlusion model in eight rats, EEG, arterial blood pressure, and body temperature were continuously controlled, In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries, During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening, The arteriole and venule diameter did not significantly change, At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 ± 229% and 233 ± 156% of their basal value, No capillary recruitment of erythrocytes was detected, All variables returned to their basal levels within less than 100 seconds after declamping, The data are discussed in terms of a possible involvement of shear stress in the reperfusion period.

Hemiballism is most commonly caused by ischemic stroke and most cases have a favorable prognosis. Lesions directly involving the subthalamic nucleus (STN) are the cause of a minority of cases but are usually associated with poor prognosis. We report two patients with a small STN lesion who presented with transient hemiballism. A small lesion confined to and only focally affecting the STN may cause hemiballism yet may have excellent outcome. Precise evaluation of the affected region with MRI is useful in predicting the prognosis.

The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

Various autoantibodies are associated with autoimmune-mediated cerebellar ataxia. Anti-Yo, -Zic, -CARPVIII, -Tr, -Ri, -Hu, -Ma, -CRMP-5, -ANNA-3, -PCA-2, -VGCC, and -mGluR antibodies (Abs) are found in paraneoplastic cerebellar ataxia, whereas anti-GAD, -thyroid, and -gliadin Abs are found in non-paraneoplastic cerebellar ataxia. Most of these antibodies are not pathogenic but are diagnostic markers. However, anti-VGCC, anti-mGluR, and anti-GAD Abs have been shown to cause cerebellar ataxia, because administration of these Abs mimics cerebellar ataxia in vivo. Experiments using in vitro preparations show that anti-VGCC Ab depresses excitatory synaptic transmissions, and anti-GAD Ab suppresses inhibitory synaptic transmissions. Anti-mGluR Ab interferes with the induction of synaptic plasticity. These results suggest that pathogenic Abs elicit cerebellar synaptic dysfunction, and thereby cause ataxia in patients.

Objective The long-term use of levodopa to treat Parkinson's disease (PD) is often limited by the development of motor complications (e.g., levodopa-induced dyskinesia, LID). We hypothesized that a non-ergot dopamine agonist with strong affinity for D3) dopamine receptors (pramipexole) may improve LID in patients taking an ergot D1/D2 dopamine agonist. Methods Patients with PD and LID being treated with levodopa in addition to an ergot dopamine agonist were randomized to either a group in which pramipexole was added to current medications or a group in which the ergot dopamine agonist was switched to pramipexole. Dyskinesia was evaluated using Core Assessment Program for Surgical Interventional Therapies scores. The unified Parkinson's disease rating scale scores, modified Hoehn and Yahr stages (at 'on' time), Parkinson's disease questionnaire-39 scores and clinical global impression-improvement scores were also used for evaluation. Results At 24 weeks, pramipexole alleviated LID with more efficiency in the switch group. Conclusion Pramipexole may be a therapeutic option for treating LID because its effects on D3 dopamine receptors may balance the D1 dopamine receptor supersensitivity associated with LID.

The significance of autoantibodies associated withneurologicalsymptoms has been the focus of interest. Recentstudies emphasized the pathogenic role of anti-gliadin antibody in gluten ataxia, an important disease of autoimmune cerebellar ataxia. To examine whether autoantibodies, including anti-gliadin antibody, play a pathogenic role, we analyzed the effects of CSF samples obtained from a Japanese patient with gluten ataxia on cerebellar synaptic transmission. Patch-clamp recordings were prepared from cerebellar Purkinje cells, the output cells from the cerebellar cortex, in mice cerebellar slices. The CSF (diluted 1:100) had no effects on the excitatory postsynaptic currents, and did not affect the release mechanisms of glutamate. These results do not support an idea that CSF autoantibodies, including anti-gliadin antibody, interfere cerebellar synaptic function so as to develop ataxia

We present a case of slowly progressive gait ataxia with a 16-year history in an 87-year-old woman. In 1994 she became aware of a slight unsteadiness while walking and cortical cerebellar atrophy was diagnosed. She had no familial history of neurological disorders. In 2007, idiopathic thrombocytopenic purpura (ITP) was diagnosed. The symptoms gradually worsened, and she was admitted in 2010 because she could not walk without support. MRI voxel-based morphometry (VBM) imaging showed atrophy of the entire cerebellum, and SPECT using eZIS showed reduced perfusion in the same regions. Her blood was positive for both anti-TPO antibody (42 IU/ml) and anti-gliadin antibody (20.2 EU). We therefore diagnosed autoimmune cerebellar atrophy. The patient showed a positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. Her posture and gait disturbance scores on the International Cooperative Ataxia Rating Scale had improved from 20 to 9. Even 16 years after onset, intravenous immunoglobulins were effective. In cases of prolonged disease, immunotherapy can be effective in autoimmune cerebellar atrophy and should not be excluded from the treatment choices.

脳虚血時に増加する線条体のグルタミン酸放出に及ぼすnitric oxide (NO) 合成酵素阻害薬の作用について検討した.Wistar ratの両側線条体にmicrodialysis probeを挿入し, 一側の線条体にはNO合成酵素阻害薬であるN-ω-nitro-L-arginine100μMを局所灌流投与し, 対側には対照のためにリンゲル液のみを灌流した.このratに14分間の一過性前脳虚血を負荷し, グルタミン酸放出量の左右差を比較した.NO合成酵素阻害薬投与側の細胞外グルタミン酸濃度は対照側に比し, 虚血時35.6%, 再灌流時59.0%の有意な高値を示した.更に, このNO合成酵素阻害薬によるグルタミン酸濃度の高値は, L-arginine500μMを同時に局所灌流投与することにより完全に抑制された.以上より, 脳局所でのNOは虚血時および再灌流時のグルタミン酸過剰放出を抑制し, グルタミン酸放出量の調節の観点からは虚血神経細胞に対して保護的に働く可能性が示唆された.

The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM) and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

A 76-year-old woman experienced unsteadiness in walking in 1996. On the basis of clinical and imaging findings, the patient was diagnosed multiple system atrophy. During follow-up, her gait disturbance became aggravated leaving her unable to walk unaided. She was referred to our department in 2003. T2-weighted images on brain magnetic resonance imaging (MRI) revealed low signal intensity in both putamina and a linear high-signal-intensity area on their outsides. Single photon emission computed tomography (SPECT) disclosed a reduced blood flow in both corpora striata. These findings were consistent with the diagnosis of Parkinsonian-type multiple system atrophy. The patient had anti-glutamic acid decarboxylase (GAD) antibody-positive type 1 diabetes mellitus and a normal thyroid function, and was positive for antithyroid antibodies. She was not found to have anemia on blood tests, but was positive for intrinsic factor antibodies. Vitamin B12 was markedly reduced to below the detection limit. The findings suggested that the patient's condition was autoimmune polyglandular syndrome type 3. In 2004, treatment with intramuscular injection of vitamin B12 was initiated, after which the patient's gait disturbance was improved and she was able to walk unaided. In 2009, her unsteady gait returned and was again unable to walk unaided. Autoimmune encephalopathy was suspected, and thus high-dose intravenous immunoglobulin therapy was performed. Following treatment she was able to walk steadily. This case suggests the importance of detailed tests for autoantibodies, including endocrine autoantibodies, and the measurement of vitamin B12 and total homocysteine levels in view of the possibility of autoimmune polyglandular syndrome-related neurological disorders in diabetic patients with intractable neurological disorders that are difficult to diagnose.

The patient, a 63-year-old man, experienced the subacute onset of chorea, for which his family doctor prescribed oral haloperidol. However, the involuntary movements gradually worsened, and the patient was referred and admitted. High-signal lesions were seen in the caudate nucleus, putamen and globus pallidus bilaterally on MRI T2-weighted and FLAIR images. Chest CT, FDG-PET and tissue biopsies also revealed that the patient had lung adenocarcinoma with multiple lymph node metastases. The patient was diagnosed as having paraneoplastic chorea associated with primary lung adenocarcinoma. Antineuronal antibodies, such as anti-CRMP-5 and anti-Yo antibodies, were absent. The patient received steroid pulse therapy, oral prednisolone therapy, and concurrent radiochemotherapy. Chorea and high-signal lesions in the corpus striatum bilaterally on MRI improved quickly, and the mediastinal lymph node swelling also improved. The patient has been stable for 3 years since the onset of his symptoms. As the prognosis of paraneoplastic chorea is relatively favorable in some patients, it should be considered in the differential diagnosis of patients with chorea.

Objective With conventional MRI and single-photon emission computed tomography (SPECT), accurate diagnosis and precise classification of cerebellar atrophy are often difficult. The objective was to verify the utility of MRI voxel-based morphometry (VBM) in combination with SPECT using easy Z-score imaging (eZIS) for diagnosing and classifying cerebellar atrophy. Patients and Methods We assessed gray matter atrophy using VBM and blood perfusion using SPECT with eZIS in fifteen patients with different types of cerebellar atrophy, such as the cerebellar variant of multiple system atrophy (MSA-C), spinocerebellar ataxia type 3 (SCA3), SCA6, and autoimmune cerebellar ataxia (AICA). Results In all five MSA-C patients, VBM imaging showed atrophy of the brainstem, the entire cerebellar vermis, and the cerebellar hemispheres, while SPECT using eZIS showed reduced perfusion in the same regions. Regarding SCA3, brainstem atrophy and reduced perfusion were recognized in two of the four patients, but none exhibited abnormal findings in the posterior lobe of the cerebellar vermis. SPECT showed that all four patients had obviously reduced perfusion in the anterior lobe of the vermis, but VBM demonstrated that there was no obvious atrophy of gray matter in any patient, meaning that the results of SPECT and VBM contradicted each other completely. All SCA6 and AICA patients exhibited atrophy and reduced perfusion in the cerebellar hemispheres but not in the brainstem. Only one AICA patient exhibited atrophy and reduced perfusion of the entire cerebellar vermis. Conclusion VBM clearly showed characteristic gray matter atrophy in the cerebellum and brainstem in different pathological conditions, thus indicating its high degree of utility in diagnosing and classifying cerebellar atrophy in combination with SPECT using eZIS.

A 52-year-old woman was admitted to the hospital because of appetite loss, unsteadiness, psychogenic symptoms, ataxia, and consciousness disturbance as a result of the ingestion of a diet restricted to only carbohydrates for a long term. Laboratory examination indicated the presence of pancytopenia with macrocytic anemia; further, decreased vitamin B1 and B12 levels were detected in her serum. Magnetic resonance imaging fluid attenuated inversion recovery (FLAIR), revealed high-signal intensity in the bilateral corpus striatum, third ventricle circumference, and cerebellar cortex. Thereafter, she received drip infusion that did not include vitamin B1 or B12 and subsequently suffered a cardiac arrest due to the aggravation of cardiac insufficiency; consequently, she was transferred to our hospital. Upon admission the patient was diagnosed to have obvious cardiomegaly with pleural effusion; further, a negative T-wave was obtained on the electrocardiogram. A diagnosis of beriberi heart disease was made because of thiamine deficiency. She was treated by thiamine administration, following which the cardiac symptoms improved immediately. Various neurological symptoms caused by encephalopathy, peripheral neuropathy and subacute combined spinal cord degeneration improved by treatment with thiamine and cyanocobalamine administration; however, some of these symptoms still remained. General awareness of the fact that neurological symptoms can be caused by vitamin deficiency is essential.

In slowly progressive cerebellar atrophy, it has been difficult to suppress the progression of cerebellar symptoms because no effective therapeutic agents are available when the diagnosis of secondary cerebellar atrophy, such as drug-induced cerebellar atrophy or paraneoplastic syndrome, is denied. However, amongst the different forms of slowly progressive cerebellar atrophy, some may be associated with treatable immune abnormalities. Therefore, we investigated the therapeutic efficacy of intravenous immunoglobulin (IVIg) in 9 patients with slowly progressive cerebellar atrophy (4 sporadic atrophy; 5 hereditary atrophy). The results were as follows. With regard to the 4 cases of sporadic atrophy, gait ataxia and imbalance were markedly improved in 1 patient who had positive anti-GAD antibody. Moderate improvement was seen in 1 patient and slight improvement in 2. With regard to the 5 cases of hereditary atrophy, gait ataxia and imbalance were moderately improved in 2 patients with SCA3, although there were 3 non-responders. In conclusion, our study results suggested that not only patients with sporadic atrophy but also some with hereditary atrophy may respond to therapy. In cases of slowly progressive cerebellar atrophy in which the cause may be due to immune abnormality, we should consider instituting active immunotherapy when a pathological state caused by immune abnormality is suspected after extensive evaluations of autoantibodies, including anti-GAD, anti-thyroid and anti-gliadin antibody, malignancy, and so on.

We reported a 31 year-old man with repeated episodes of migraine at a frequency of about once a week on and after January, 2000. In January 2001, scintillating scotoma and pulsating headache appeared followed by left hemianopsia. His platelet count decreased to 80,000/microliter and high intensity areas were observed in the right occipital lobe and hippocampal gyrus on the FLAIR image of brain MRI. Subsequently performed brain MRA and vertebral angiography revealed segmental stenosis and obstruction in the right posterior cerebral artery. Under the diagnosis of migrainous infarction, sodium ozagrel and lomerizine hydrochloride were administered. Idiopathic thrombocytopenic purpura was additionally diagnosed based on the decreased platelet count which was then treated with predonisolone. After these treatment, his migraine attack disappeared. In this patient, platelet destruction due to idiopathic thrombocytopinic purpura and subsequent release of serotonin seemed to have involved in the occurrence of migrainous infarction.

Background and Purpose —The present study was designed to investigate whether neuronally derived nitric oxide (NO) plays a toxic role in the cascade of cellular events triggered by global cerebral ischemia in rats. Methods —7-Nitroindazole (7-NI) was used as a selective inhibitor of neuronal NO synthase. Global ischemia was induced for 20 minutes in anesthetized rats following the four-vessel occlusion model. Electroencephalogram and brain and body temperatures were continuously monitored. All rats were thermoregulated for the entire duration of anesthesia. 7-NI (25 mg/kg) or its vehicle was given intraperitoneally just after the carotid clamping and again 1 hour later. Rats were randomly divided into four groups: (1) vehicle (n=7); (2) 7-NI (n=7); (3) l -arginine (300 mg/kg IP)+7-NI (n=7); and (4) 7-NI associated with warming to 37°C for 7 hours after disruption of anesthesia to compensate for the decrease in temperature induced by 7-NI (n=9). Seven days after ischemia, hippocampal CA1 damage was evaluated by classic histology. The lesion was scored with the use of a point scale, and the surviving neurons were counted. Results —Lesion scores were significantly lower and neuron counts higher in the two (warmed and unwarmed) groups of rats in which 7-NI was given alone than in vehicle- and l -arginine+7-NI–treated rats. Conclusions —The results indicate that 7-NI was neuroprotective in 20-minute global ischemia in rats and that the neuroprotective effect of 7-NI was mostly due to the blockade of NO synthesis, suggesting that NO released from neurons in ischemic conditions has a deleterious influence on hippocampal pyramidal neurons.

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-d-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 ± 15.8 μ M (mean ± SD) to 21.4 ± 11.4 μ M (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 ± 5.8 to 19.9 ± 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.

In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias., SCOPUS: re.j, info:eu-repo/semantics/published